title: Nitric oxide synthases are crucially involved in the development of the severe cardiomyopathy of caveolin-1 knockout mice.
abstract: Targeted ablation of caveolin-1 (cav-1) results in a severe cardiomyopathy. How the loss of cav-1 mediates these abnormalities is currently under investigation. Mounting evidence indicates that cav-1 acts as a negative regulator of endothelial nitric oxide synthase resulting in a constitutive hyperactivation of the nitric oxide (NO)-pathway in cav-1 knockout mice (cav-1 ko). In this context we hypothesized that disturbed NO signalling is implicated in these changes. To explore this question cav-1 ko were compared with knockout counterparts experiencing 2 month postnatal NO synthase inhibition by N(G)-nitro-l-arginine methyl ester (l-NAME) treatment. Chronic l-NAME treatment resulted in significant improvements in heart function and exercise capacity in cav-1 ko. Furthermore, we found evidence for an enhanced radical stress in hearts of cav-1 ko which was markedly reduced by l-NAME treatment. Collectively, these findings suggest that NO synthases play a crucial role in the evolution of heart failure evident in cav-1 ko.
authors.affiliation: University of Technology Dresden, Department of Medicine and Cardiology, Medical Clinic, Fetscherstr. 76, Dresden 01307, Germany. carstenwunderlich@gmx.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Wunderlich
authors.forename: Kristin
authors.initials: K
authors.lastname: Schober
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
authors.forename: Christian
authors.initials: C
authors.lastname: Heerwagen
authors.forename: Rainer
authors.initials: R
authors.lastname: Marquetant
authors.forename: Bernd
authors.initials: B
authors.lastname: Ebner
authors.forename: Matthias
authors.initials: M
authors.lastname: Forkmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Schoen
authors.forename: Ruediger C
authors.initials: RC
authors.lastname: Braun-Dullaeus
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmeisser
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051242:Caveolin 1 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D013481:Superoxides / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D004791:Enzyme Inhibitors; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester